This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Degradation/Utilization/Assimilation → Aldehyde Degradation|
|Detoxification → Methylglyoxal Detoxification|
Methylglyoxal is produced in small amounts during glycolysis (via glycerone phosphate), fatty acid metabolism (via acetone), and protein metabolism (via aminoacetone). Methylglyoxal is highly toxic, most likely as a result of its interaction with protein side chains (see [Kalapos99] for a review). There are several pathways for the detoxification of methylglyoxal, based on different enzymes that are able to convert methylglyoxal to less toxic compounds. These enzymes include glyoxalase enzymes, methylglyoxal reductases, aldose reductases, aldehyde reductases and methylglyoxal dehydrogenases.
About This Pathway
The glyoxalase system is probably the most common pathway that catalyzes the conversion of methylglyoxal to a less toxic product. In this pathway, methylglyoxal is converted to (R)-lactate via the intermediate (R)-S-lactoylglutathione by 2 enzymes:
glyoxalase I isomerizes the hemithioacetal that is formed non-enzymatically from methylglyoxal and glutathione to (R)-S-lactoylglutathione. glyoxalase II hydrolyzes the thioester to (R)-lactate regenerating the glutathione in the process.
The fate of (R)-lactate has been less well characterized. The most likely scenario is its conversion to pyruvate by the action of D-lactate dehydrogenase, a flavoprotein specific to the D-form of lactate [Olson79, Flick02].
The pathway is ubiquitous in biological life, taking place in the cytosol of prokaryotes and the mitochondria of eukaryotes [Ewaschuk05].
Superpathways: superpathway of methylglyoxal degradation
Variants: methylglyoxal degradation II, methylglyoxal degradation III, methylglyoxal degradation IV, methylglyoxal degradation V, methylglyoxal degradation VI, methylglyoxal degradation VII, methylglyoxal degradation VIII
Unification Links: EcoCyc:PWY-5386
Barnes70: Barnes EM, Kaback HR (1970). "Beta-galactoside transport in bacterial membrane preparations: energy coupling via membrane-bounded D-lactic dehydrogenase." Proc Natl Acad Sci U S A 66(4);1190-8. PMID: 4394455
Barnes71: Barnes EM, Kaback HR (1971). "Mechanisms of active transport in isolated membrane vesicles. I. The site of energy coupling between D-lactic dehydrogenase and beta-galactoside transport in Escherichia coli membrane vesicles." J Biol Chem 1971;246(17);5518-22. PMID: 4330922
Bito97: Bito A, Haider M, Hadler I, Breitenbach M (1997). "Identification and phenotypic analysis of two glyoxalase II encoding genes from Saccharomyces cerevisiae, GLO2 and GLO4, and intracellular localization of the corresponding proteins." J Biol Chem 272(34);21509-19. PMID: 9261170
Bito99: Bito A, Haider M, Briza P, Strasser P, Breitenbach M (1999). "Heterologous expression, purification, and kinetic comparison of the cytoplasmic and mitochondrial glyoxalase II enzymes, Glo2p and Glo4p, from Saccharomyces cerevisiae." Protein Expr Purif 17(3);456-64. PMID: 10600466
Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043
CamposBermudez10a: Campos-Bermudez VA, Gonzalez JM, Tierney DL, Vila AJ (2010). "Spectroscopic signature of a ubiquitous metal binding site in the metallo-β-lactamase superfamily." J Biol Inorg Chem 15(8);1209-18. PMID: 20535505
Clugston04: Clugston SL, Yajima R, Honek JF (2004). "Investigation of metal binding and activation of Escherichia coli glyoxalase I: kinetic, thermodynamic and mutagenesis studies." Biochem J 377(Pt 2);309-16. PMID: 14556652
Clugston98: Clugston SL, Barnard JF, Kinach R, Miedema D, Ruman R, Daub E, Honek JF (1998). "Overproduction and characterization of a dimeric non-zinc glyoxalase I from Escherichia coli: evidence for optimal activation by nickel ions." Biochemistry 1998;37(24);8754-63. PMID: 9628737
Davidson01: Davidson G, Clugston SL, Honek JF, Maroney MJ (2001). "An XAS investigation of product and inhibitor complexes of Ni-containing GlxI from Escherichia coli: mechanistic implications." Biochemistry 40(15);4569-82. PMID: 11294624
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Fung79: Fung LW, Pratt EA, Ho C (1979). "Biochemical and biophysical studies on the interaction of a membrane-bound enzyme, D-lactate dehydrogenase from Escherichia coli, with phospholipids." Biochemistry 1979;18(2);317-24. PMID: 369600
GeorgeNasciment76: George-Nascimento C, Wakil SJ, Short SA, Kaback HR (1976). "Effect of lipids on the reconstitution of D-lactate oxidase in Escherichia coli membrane vesicles." J Biol Chem 251(21);6662-6. PMID: 789373
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